Cancer, which are a series of diseases characterized in abnormal cell proliferation and metastasis, has been one of the serious diseases that threaten the human health. According to the statistics from WTO, about 6 million peoples suffer newly from cancer every year all over the world. In China, cancer has been the second largest cause of death after cardiacerebral vascular diseases.
In the field of chemical treatment for tumor, effective drugs against various cancers have been studied for a long time. But unfortunately, although the developed anti-cancer drugs can kill cancer cells effectively, they are greatly toxic to normal cells. Patients taking those drugs showed weight loss, nausea, hallucinations, loss of appetite and other symptoms. In addition, the current chemotherapeutic agents can not provide ideal effects and broad-spectrums against tumors. Therefore, there is an urgent need for developing a chemotherapeutic agent, which can effectively treat various cancers with high selectivity and high efficiency.
Bengamides are a class of natural products from the ocean, which have significant antineoplasmic activities. Since the compounds were isolated from the marine sponge in 1986, their synthesis has been studied by a plural of research groups due to their extensive biological activities. Among them, bengamide B has the most prominent antineoplasmic activities, which shows activities against human tumor cells at a nanomolar level in all of the in vitro tests, and also can remarkably depress the growth of heterograft of MDA-MB-4355 human breast cancer cells in vivo. Since bengamide B has defects such as poor solubility, difficulties in synthesis, etc, Novartis performed a study on the synthesis of Bengamide analogues in 2001, and developed an analogue of the natural Bengamide B, LAF389, which has a good solubility, and activities in vitro and in vivo comparable to Bengamide B. Although LAF389 showed a good prospect in its initial stage, after it entered clinical study at 2001, it was found that the compound had side effects such as taste disturbance, blurred vision, etc., and did not possess the foreseen therapeutic effects, making no further development be performed.
